Scaffold-Mediated Organization of Signal Transduction Networks

dc.contributor.advisorWhite, Michael A.en
dc.creatorBumeister, Ronalden
dc.date.accessioned2010-07-12T17:35:43Z
dc.date.available2010-07-12T17:35:43Z
dc.date.issued2004-08-19
dc.description.abstractThe Raf-MEK-ERK kinase cascade is a highly conserved signal transduction module involved in cellular processes ranging from proliferation and differentiation to transformation and apoptosis, and is engaged in response to growth factors, cytokines, morphogens, and other extracellular stimuli. Given the ubiquitous nature of this signaling pathway, it is not clear how specialization with respect to various Raf-dependent phenomena is acquired. In theory, functional specificity could be achieved by selectively coupling the core enzymatic components of a cascade to other regulatory pathways depending on the cellular context. Here, by using loss-of-function and partial loss-of-function mutant analysis, we demonstrate that Raf can participate in cell regulatory processes independently of its ability to activate MEK. We also show that scaffolding proteins can serve as specificity determinants in Ras/MAPK signaling, and may function to coordinate the activity of this cascade with additional regulatory pathways required for an appropriate biological response. Thus, we provide evidence for functional diversification both at the level of Raf substrates and at the level of molecular organization by accessory scaffolding molecules.en
dc.format.digitalOriginborn digitalen
dc.format.mediumElectronicen
dc.format.mimetypeapplication/pdfen
dc.identifier.oclc59226627
dc.identifier.urihttps://hdl.handle.net/2152.5/325
dc.language.isoenen
dc.subjectProtamine Kinaseen
dc.subjectCell Physiological Processesen
dc.subjectSignal Transductionen
dc.titleScaffold-Mediated Organization of Signal Transduction Networksen
dc.typeThesisen
dc.type.genredissertationen
dc.type.materialTexten
thesis.date.available2008-08-19
thesis.degree.departmentGraduate School of Biomedical Sciencesen
thesis.degree.disciplineCell Regulationen
thesis.degree.grantorUT Southwestern Medical Centeren
thesis.degree.levelDoctoralen
thesis.degree.nameDoctor of Philosophyen

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